About 31 million adults and children are estimated to have been infected with HIV worldwide, and about 21 million (68%) of all infections are assumed to be in sub-Saharan Africa. It is also estimated that 80% of all female HIV infections worldwide are in sub-Saharan Africa. In Malawi, the prevalence of HIV is 30% among pregnant women, the incidence of HIV is about 4 per 100 person-years among women of reproductive age, and infant mortality is more than 100 per 1000 live births. The rate of mother to child transmission of HIV is about 28%. Several risk factors such as sexually transmitted diseases (STDs) have been shown to be associated with HIV. Low-cost, sustainable, and practical intervention measures are urgently needed. The Malawi research team intends to work closely with the HIV Prevention Trials Network (HPTN) leadership and other HIV Prevention Trials Units (HPTUs) investigators to develop and implement research protocols which advance the network agenda of HIV prevention in developing and developed countries. The Johns Hopkins University (JHU), University of North Carolina (UNC)-CH, and College of Medicine (COM), University of Malawi collaboration has made a variety of contributions to HIV prevention in virtually all research areas of interest to the HPTN. In addition, through the HIVNET and other sources we have developed the resources and infrastructure to conduct large HIV intervention trials critical to the success of the new network. The specific aims of this application are to contribute to the HPTN research, to demonstrate the capability to conduct HIV prevention research in Malawi, and to expand and include additional populations as required for multiple, concurrent efficacy trials. The collaboration of JHU, UNC, and Malawi COM, the experience of the investigators and the research findings they have generated from previous work in Malawi, and the existing infrastructure, will serve the site to contribute to the HPTN research and prevention objectives. Consistent with the HPTN research direction, the Malawi investigators have carried out successful innovative perinatal, microbicide, STD, nutritional supplementation, and other studies. Currently, two major HIVNET phase III clinical trials involving a study on the effectiveness of the microbicide N-9 to prevent acquisition of HIV and STDS, and the efficacy of a perinatal intervention trial combining nevirapine and antibiotic treatment of chorioamnionitis are in progress. We intend to continue these studies and to expand to additional sites.